Nakamura T, Suzuki A, Ohnuki T, Hattori K, Watanabe K, Kurose H, Nagao T, Nagatomo T
Department of Pharmacology, Niigata College of Pharmacy, Niigata, Japan.
Pharmacology. 2000 Jul;61(1):6-10. doi: 10.1159/000028373.
This study was performed to assess the affinities of propranolol, bopindolol, its two metabolites (18-502, 20-785), pindolol, metoprolol, and atenolol to beta(1)- and beta(2)-adrenoceptor (beta(1)- and beta(2)-AR) subtypes using the membranes of COS-7 cells transiently expressing beta(1)- and beta(2)-AR subtypes. Radioligand-binding assays were performed and the results were compared with those (pKi or pA(2) values) obtained from the membrane-enriched fractions from the rat heart, cerebral cortex, bovine heart, tracheal smooth muscle or guinea-pig heart muscle. The pKi values of propranolol, bopindolol, its two metabolites, atenolol, pindolol and metoprolol to beta(1)-AR subtypes obtained from COS-7 cell membranes were 9.02 +/- 0.04, 7.44 +/- 0.12, 9.38 +/- 0.31, 6. 65 +/- 0.16, 5.55 +/- 0.14, 8.17 +/- 0.15 and 5.99 +/- 0.13, respectively. The rank order of pKi values for these agents to beta-(2)-ARs in COS-7 cell membranes was the same as that of beta(1)-ARs. In addition, good correlations were observed between pKi values of homogenates from various tissues and those of transfected COS-7 cell membranes to beta(1)- and beta(2)-ARs. Although good correlations were also observed between pA(2) values obtained from tracheal smooth muscle (beta(2)-ARs) and pKi values obtained from transfected COS-7 cell membranes to beta(2)-ARs, low correlation coefficient values to beta(1)-ARs were observed, however. In conclusion, these results suggested that binding characteristics of (3)H-CGP-12177 to beta-AR subtypes in these membranes from transfected COS-7 cells are similar to those from membrane fractions of various tissues.
本研究旨在利用瞬时表达β₁-和β₂-肾上腺素能受体（β₁-和β₂-AR）亚型的COS-7细胞膜，评估普萘洛尔、波吲洛尔及其两种代谢产物（18-502、20-785）、吲哚洛尔、美托洛尔和阿替洛尔与β₁-和β₂-肾上腺素能受体亚型的亲和力。进行了放射性配体结合试验，并将结果与从大鼠心脏、大脑皮层、牛心脏、气管平滑肌或豚鼠心肌的富含膜的组分中获得的结果（pKi或pA₂值）进行比较。从COS-7细胞膜获得的普萘洛尔、波吲洛尔及其两种代谢产物、阿替洛尔、吲哚洛尔和美托洛尔对β₁-AR亚型的pKi值分别为9.02±0.04、7.44±0.12、9.38±0.31、6.65±0.16、5.55±0.14、8.17±0.15和5.99±0.13。这些药物在COS-7细胞膜中对β₂-ARs的pKi值的排序与β₁-ARs相同。此外，观察到来自各种组织的匀浆的pKi值与转染的COS-7细胞膜对β₁-和β₂-ARs的pKi值之间具有良好的相关性。然而，虽然在气管平滑肌（β₂-ARs）获得的pA₂值与转染的COS-7细胞膜对β₂-ARs获得的pKi值之间也观察到良好的相关性，但对β₁-ARs的相关系数值较低。总之，这些结果表明，在转染的COS-7细胞的这些膜中，³H-CGP-12177与β-AR亚型的结合特性与来自各种组织膜组分的结合特性相似。
